1. Field of the Invention
This invention relates to a novel depsipeptide containing N-substituted glycine residue and a pharmaceutical composition containing the same as an active ingredient. The depsipeptides of the invention have a promoting activity on the production of apolipoprotein E and are useful as therapeutic agents for neurologic damages, especially dementia, and hyperlipemia.
2. Description of the Prior Art
As a therapeutic agent for senile dementia, there have been mainly applied activators of cerebral circulation and metabolism, but these drugs have no improving effect on disintegration of the central nervous system which is believed to cause senile dementia. Consequently, they do not show any improving effect on dysmnesia or acalculia which is said to be the main symptom of dementia. In view of this, there has been desired a drug as a new type of the therapeutic agent for senile dementia which may promote the repair and growth of nervous systems while inhibiting the disintegration of the central nervous system. On the other hand, it has been reported that apolipoprotein E may be generated at a high level at the damaged sites of nervous systems which are being repaired (For example, refer to M. J. Igunatius et al., Proc. Natl. Acad. Sci. U.S.A., 83, 1125 (1986)). This suggests that apolipoprotein E will play an important role in repairing the damaged nervous systems.
Moreover, it has recently been reported that a remarkable reduction in a plasma cholesterol level can be observed when apolipoprotein E is administered intravenously to WHHL rabbit, which is a model animal for human familial hypercholesterolemia homozygote (Yamada et al., Proceeding of National Academy Science USA, Vol. 86, pp. 665-669, 1989). Also, it has been reported that plasma cholesterol and plasma triglyceride can be noticeably decreased by transducing a gene for apolipoprotein E into the mouse liver and expressing apolipoprotein E in a large mass (Shimano, H. et al., Journal of Clinical Investigation, Vol. 90, pp. 2084-2091, 1992).
As is apparent from these reports, the increase in plasma apolipoprotein E concentration has been regarded as extremely effective in the treatment of hyperlipemia, especially familial hypercholesterolemia homozygote which has been hitherto considered as difficult to be treated with the prior art drugs.